Studies On The Synthesis, Characterization And The DNA Recognition Properties Of Novel Ruthenium (Ⅱ) Complexes

DNA is the inherited substance in the life, and it's one of the mainly target in antitumor drugs, which is decided by specifically base sequences and strict base partnership principle. It is important for studying of interaction mode with antitumor drug in vivo to the specified interaction between the small molecule and biological great molecule. More and more research confirmed that the antitumor activity and toxicity of many drugs correlate to the selectivity of DNA, and study on the DNA recognition properties, the structure and construct analyses of DNA-complex have become significant composing parts to evaluate the antitumor drug. The aims of this paper are design, synthesis and characteristic a series of novel ruthenium polypyrdyl complexes as the target in vitro of DNA, and studies these complexes DNA-binding active by using ultraviolet visible absorption spectroscopy, fluorescent spectrum and CD spectra. It has been supplied model evidence to the interaction mode and site of between drug molecule and biological great molecule. And the complexes have been subjected to activity study against tumor cell in vitro. This dissertation consists of six chapters.In chapter 1, the significance of study about metal antitumor drugs in cancer therapy are first described, At the same time, the used methods of the interaction between anticancer drugs are introduced, and antitumor action mechanism of metal ruthenium complexes are also detailed reviewed. With these described above as basis, the purposes of this article are suggested. In chapter 2, we illuminate the design idea of target complexes by systemic reviewing about structure categories of ruthenium complexes as the antitumor drugs in recent ten years.In chapter 3 and 4, the synthesis and characteristic are detailed discussed about enantiomeric ruthenium complexesΔ(Λ)-Ru(bpy)₂L (bpy=2,2'-bipyridine, L=PYNI, HPIP, FPIP, IPBP) and ruthenium polypyrdyl complexes Ru(phen)₂L(phen= 1,10-phenanthroline, L= CPIP, MHPIP, HMPIP, FPIP), and these complexes DNA-binding active were studied by using ultraviolet visible absorption spectroscopy, fluorescent spectrum. The result indicates that DNA have the enantiomeric recognition properties, and observed dextrorotary complexes have stronger activity as binding DNA than laevogyrate ones. It has been found that the DNA binding of these complexes are relevant to the structure of ligands, hydrogen bonds effect and space hindrance.In chapter 5, the synthesized enantiomeric ruthenium complexes were tested for their inhibitory activity towards tumor cell in vitro by MTT method, The result indicate that complexes [Ru(bpy)₂(FPIP)]²⁺ have better inhibitory activity than 5-FU and other target complexes against tumor cells the liver carcinoma (BEL-7402). In the finally chapter, the research status of a series of ruthenium complexes are summarized.